The Johns Hopkins Drug Abuse Research Center focuses on the Dynamics of Signaling by Molecular Messengers Relevant to Actions of Drugs of Abuse, an approach, which, over the years, has led to major insights into how novel proteins and small molecular messengers provide the neuronal signaling which underlies actions of psychotropic drugs. The ongoing and proposed projects of the four principal investigators interdigitate and are notably synergistic. Snyder addresses novel molecular messengers underlying drug actions including (1) NO/GAPDH nuclear signaling (2) Inositol hexakisphosphate kinase-2 (IP6K2) impacting cell death and neurotoxicity and (3) Actions of inositol polyphosphate multikinase (IPMK) that impact brain function. Worley deals with Rheb1 and mTOR signaling with a focus on (1) Translational mechanisms and transcriptional events regulated by mTOR, (2) The role of Rheb1 in myelination in the brain and (3) LanCL1 impacting signaling and growth factor dependent neuronal survival. The Dawsons address dynamics of poly (ADP-ribose) and how it regulates maladaptive stress responses that occur with psychotropic drug action. Specific areas of interest include (1) Iduna, a major novel protein regulating poly(ADP-ribose) disposition and cell survival, (2) Iduna influences upon epigenetic modifications (3) Influences of Iduna upon microRNA processing. Baraban deals with how the translin/trax RNAse complex regulates microRNA processing and responses to cocaine with a focus upon (1) Identifying physiologic targets of translin/trax, (2) Determining how deletion of translin interfaces with signaling pathways that are regulated by cocaine, and (3) Elucidating how striatal translin affects behavioral responses to cocaine.

Public Health Relevance

The Hopkins Drug Abuse Research Center focuses on molecular messengers whose actions are relevant to effects of abusable drugs. Discoveries by the Hopkins investigators have elucidated novel signaling systems that explain the neurotoxic effects of many drugs. These efforts have also uncovered new ways whereby cocaine exerts its psychoactivity. CENTER CHARACTERISTICS:

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
4P50DA000266-45
Application #
9067336
Study Section
Special Emphasis Panel (ZDA1)
Program Officer
Pollock, Jonathan D
Project Start
1975-06-20
Project End
2017-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
45
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Paul, Bindu D; Snyder, Solomon H (2018) Gasotransmitter hydrogen sulfide signaling in neuronal health and disease. Biochem Pharmacol 149:101-109
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Hinkle, Jared T; Perepezko, Kate; Mills, Kelly A et al. (2018) Dopamine transporter availability reflects gastrointestinal dysautonomia in early Parkinson disease. Parkinsonism Relat Disord 55:8-14
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Hinkle, Jared T; Perepezko, Kate; Rosenthal, Liana S et al. (2018) Markers of impaired motor and cognitive volition in Parkinson's disease: Correlates of dopamine dysregulation syndrome, impulse control disorder, and dyskinesias. Parkinsonism Relat Disord 47:50-56
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Chern, Yijuang; Chien, Ting; Fu, Xiuping et al. (2018) Trax: A versatile signaling protein plays key roles in synaptic plasticity and DNA repair. Neurobiol Learn Mem :
Vasavda, Chirag; Zaccor, Nicholas W; Scherer, Paul C et al. (2017) Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding. J Vis Exp :
Park, Alan Jung; Havekes, Robbert; Fu, Xiuping et al. (2017) Learning induces the translin/trax RNase complex to express activin receptors for persistent memory. Elife 6:
Fu, Chenglai; Xu, Jing; Cheng, Weiwei et al. (2017) Neuronal migration is mediated by inositol hexakisphosphate kinase 1 via ?-actinin and focal adhesion kinase. Proc Natl Acad Sci U S A 114:2036-2041

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